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Title page for ETD etd-01282010-163632

Type of Document Dissertation
Author Gruver, Jonathan Scott
Author's Email Address scott.gruver@vanderbilt.edu
URN etd-01282010-163632
Title Towards a Unified Understanding of Eukaryotic Cell Motility
Degree PhD
Department Pharmacology
Advisory Committee
Advisor Name Title
Alex Brown Committee Chair
Brian Wadzinski Committee Member
Chang Chung Committee Member
Roger Colbran Committee Member
Todd Graham Committee Member
  • cell motility
Date of Defense 2009-10-22
Availability unrestricted
Cell motility plays important roles in development, wound healing, and metastasis. Cells move either spontaneously, in a non-directed fashion, or in response to chemotactic signals, in a directed fashion. Even though they are often studied separately, both forms of motility share many complex processes at the molecular and subcellular scale, e.g., orchestrated cytoskeletal rearrangements and polarization. In addition, at the cellular level both types of motility include directionally persistent runs interspersed with reorientation pauses. The non-directed and chemotactic motility of Dictyostelium cells was studied quantitatively. Focusing first on chemotaxis, it was discovered that cells coordinate their speed and direction to increase chemotactic efficiency. Application of bimodal analysis, a method that compares time spent in persistent mode versus reorientation mode, to non-directed and chemotactic motility revealed that reorientation time is coupled with persistent time in an inverse correlation. Surprisingly, the inverse correlation holds for both non-directed and chemotactic motility so that the full range of Dictyostelium motility can be described by a single scaling relationship. Additionally, we found an identical scaling relationship for three human cell lines, indicating that the coupling of reorientation holds across species and making it possible to describe the complexity of cell motility in a surprisingly general and simple manner. We speculate that spontaneous cell polarity and the resultant directional persistence to be a fundamental aspect of cell motility that is quantitatively tuned by the presence of chemoattractant-induced signaling to increase chemotactic efficiency.
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